The organism is inhabited by antioxidizing enzymes and antioxidizing substances that function to prevent pathologically excessive occurrence of free radicals or eliminate the free radicals suffered to occur at all. It is known that on the intestinal mucous membranes of patients of such inflammatory bowel diseases as ulcerative colitis and Crohn's disease, such antioxidizing enzymes and antioxidizing substances as superoxide dismutase (SOD), glutathione, and .alpha.-tocopherol are consumed till shortage of supply (G. G. Buffinton and W. F. Doe: Free Radic. Biol. Med., 19 (1995) 911-918). It is believed that the reinforcement of the antioxidation protecting system by the administration of a medicine capable of resisting oxidation is effective in preventing and curing these diseases.
The free radicals, as aptly called a "double-edged sword," not only function to give rise to a morbid condition but also prove very important for a biophylactic system. Mere elimination of all the free radicals is hardly feasible. This fact constitutes itself the largest cause for making difficult the clinical application of the free radical resistance therapy.
Of the medicines which possess an antioxidizing action, those which have been already accepted for clinical application as an internal curative agent for ulcerative colitis and Crohn's disease include classic steroid chemicals and salazosulfapyridine (SASP, Salazopyrin) and those which have been undergoing a basic study include SOD preparations such as Mn-SOD and CuZn-SOD, zinc preparations such as allopurinol and porapurezinc [sic], .alpha.-tocopherol, glutathione, glutathione peroxidase, and 21-aminosteroid, herbal medicines such as sigyakusan [sic] and rebamipido [sic].
Particularly, (.alpha.-tocopherol is a typical entity of vitamin E, possesses a function of eliminating free radicals by supplying a hydrogen atom from the hydroxyl group at the 6 position of a chromane ring thereof, and has earned fame as an antioxidizing agent.
The vitamin E, however, is a viscous oily substance not soluble in water because it has a long-chain hydrocarbon group (phytyl group) in the molecular unit thereof. When the vitamin E is to be administered for the purpose of repressing and controlling the free radicals in the organism, therefore, it betrays a fatal disadvantage of not allowing itself to be used in the form of a solution like an internal medicine or an injection. To overcome this weak point, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid which is endowed with water-solubility by the substitution of the phytyl group at the 2 position with a carboxyl group has been developed. It is commercially offered as a water-soluble antioxidizing agent under the designation of "Trolox." The water-solubility of this agent is extremely low (about 15 mg/100 ml) and fails to achieve full satisfaction. For the same reason, 2-hydroxymethyl-2,5,7,8-tetramethylchroman-6-ol resulting from the substitution of the phytyl group at the 2 position with an alcohol (hereinafter referred to as "TMC-2-substituted methanol") has been developed. This TMC-2-substituted methanol possesses water-solubility of about 100 mg/100 ml, a value about 6.3 times that of Trolox. In spite of this relatively high water-solubility, the administration of 1 g of this compound to a patient, for example, requires the compound to be used as dissolved in such a large amount of water as 1 liter. The TMC-2-substituted methanol, therefore, still encounters the problem of offering no fully satisfactory water-solubility.
This invention, produced in view of the problem of prior art described above, has for an object thereof the provision of a novel preventive and curative agent for inflammatory diseases, which manifests the effect at a low application rate without entailing a side effect in preventing the inflammatory diseases or ameliorating and curing them.
Another object of this invention is to provide a novel preventive and curative agent for inflammatory bowel diseases, which possesses a fine antioxidizing action such as to bring effective repression and control of a free radical reaction possibly occurring on the intestinal mucous membrane at the site of an inflammatory bowel disease.
Still another object of this invention is to provide a novel preventive and curative agent for inflammatory bowel diseases, which is capable of repressing development of cell adhesion molecules and reducing humectation of the tissue with neutrophil.
Yet another object of this invention is to provide a novel preventive and curative agent for inflammatory bowel diseases, which can be formulated as an aqueous preparation containing the active ingredient thereof in a high concentration.